Macrophage-Inducible C-Type Lectin/Spleen Tyrosine Kinase Signaling Pathway Contributes to Neuroinflammation After Subarachnoid Hemorrhage in Rats

He, Yue; Xu, Liang; Li, Bo; Guo, Zhen‐Ni; Hu, Qin; Guo, Zongduo; Tang, Juan; Chen, Yujie; Zhang, Yang; Tang, Jiping; Zhang, Junyi

doi:10.1161/strokeaha.115.010088

Cited by 72 publications

(74 citation statements)

References 37 publications

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“…The findings are consistent with those of recently reported studies that have shown increased Mincle expression in the brains of humans and rodents after brain injury (14,15). These data, as well as the data presented here, allowed us to hypothesize that the Mincle may be an important sensor of nonphysiological cell death or cell stress that recognizes endogenous molecules released from damaged tissues and subsequently induces inflammation.…”

Section: Mincle Is a Prr In The Skin That Is Highly Inducible In Respsupporting

confidence: 93%

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

Kostarnoy

Gancheva

Lepenies

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Sterile (noninfected) inflammation underlies the pathogenesis of many widespread diseases, such as allergies and autoimmune diseases. The evolutionarily conserved innate immune system is considered to play a key role in tissue injury recognition and the subsequent development of sterile inflammation; however, the underlying molecular mechanisms are not yet completely understood. Here, we show that cholesterol sulfate, a molecule present in relatively high concentrations in the epithelial layer of barrier tissues, is selectively recognized by Mincle (Clec4e), a C-type lectin receptor of the innate immune system that is strongly up-regulated in response to skin damage. Mincle activation by cholesterol sulfate causes the secretion of a range of proinflammatory mediators, and s.c. injection of cholesterol sulfate results in a Mincle-mediated induction of a severe local inflammatory response. In addition, our study reveals a role of Mincle as a driving component in the pathogenesis of allergic skin inflammation. In a well-established model of allergic contact dermatitis, the absence of Mincle leads to a significant suppression of the magnitude of the skin inflammatory response as assessed by changes in ear thickness, myeloid cell infiltration, and cytokine and chemokine secretion. Taken together, our results provide a deeper understanding of the fundamental mechanisms underlying sterile inflammation.innate immunity | sterile inflammation | allergy | Mincle | cholesterol sulfate

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Section: Mincle Is a Prr In The Skin That Is Highly Inducible In Respsupporting

confidence: 93%

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

Kostarnoy

Gancheva

Lepenies

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The data indicate that MK is a genetic factor that regulates the neuroinflammatory effects induced by this type of psychostimulants. In this context, it is also important to note that MK expression and signaling are activated in the brain after administration of different drugs of abuse [33–35]. Taking together, our data suggest that the previously shown neuroprotective effects of MK against drug-induced neurotoxicity [20, 36] could be related to its ability to prevent neuroinflammation.…”

Section: Discussionsupporting

confidence: 54%

Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

Vicente-Rodríguez

Fernández-Calle

Gramage

et al. 2016

Mediators of Inflammation

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Midkine (MK) is a cytokine that modulates amphetamine-induced striatal astrogliosis, suggesting a possible role of MK in neuroinflammation induced by amphetamine. To test this hypothesis, we studied astrogliosis and microglial response induced by amphetamine (10 mg/kg i.p. four times, every 2 h) in different brain areas of MK−/− mice and wild type (WT) mice. We found that amphetamine-induced microgliosis and astrocytosis are enhanced in the striatum of MK−/− mice in a region-specific manner. Surprisingly, LPS-induced astrogliosis in the striatum was blocked in MK−/− mice. Since striatal neuroinflammation induced by amphetamine-type stimulants correlates with the cognitive deficits induced by these drugs, we also tested the long-term effects of periadolescent amphetamine treatment (3 mg/kg i.p. daily for 10 days) in a memory task in MK−/− and WT mice. Significant deficits in the Y-maze test were only observed in amphetamine-pretreated MK−/− mice. The data demonstrate for the first time that MK is a novel modulator of neuroinflammation depending on the inflammatory stimulus and the brain area considered. The data indicate that MK limits amphetamine-induced striatal neuroinflammation. In addition, our data demonstrate that periadolescent amphetamine treatment in mice results in transient disruption of learning and memory processes in absence of endogenous MK.

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“…Specifically, Mincle expression was found to be upregulated during ischemic stroke, whereas inhibition of Mincle signaling via Syk blockade led to a significant decrease in the volume of cerebral infarct and brain swelling 34 . Similarly, Mincle signaling affects neuro-inflammation after subarachnoid hemorrhage and traumatic brain injury 35, 36 . Mincle deletion has also been shown to mitigate obesity-induced insulin resistance in mice fed high-fat diets 37 .…”

Section: Discussionmentioning

confidence: 99%

Mincle Signaling Promotes Con A Hepatitis

Greco

Torres‐Hernandez

Kalabin

et al. 2016

The Journal of Immunology

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Concanavalin-A (Con-A) hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor (CLR) that is critical in the immune response to mycobacteria and fungi, but does not have a well-defined role in pre-clinical models of non-pathogen mediated inflammation. Since Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con-A hepatitis. Acute liver injury was assessed in the murine Con-A hepatitis model using C57BL/6, Mincle−/−, and Dectin-1−/− mice. The role of C/EBPβ and HIF-1α signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con-A hepatitis. Most significantly, Mincle deletion or blockade protected against Con-A hepatitis whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other CLRs did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ related signaling intermediates, C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con-A hepatitis and inhibition of both C/EBPβ and HIF1-α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con-A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.

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Macrophage-Inducible C-Type Lectin/Spleen Tyrosine Kinase Signaling Pathway Contributes to Neuroinflammation After Subarachnoid Hemorrhage in Rats

Cited by 72 publications

References 37 publications

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

Mincle Signaling Promotes Con A Hepatitis

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